Practice Parameter

Adverse reactions to vaccinesChief Editors: John M. Kelso, MD and James T. Li, MD, PhD

Co-Editors: Richard A. Nicklas, MD; Joann Blessing-Moore, MD; Linda Cox, MD;David M. Lang, MD; John Oppenheimer, MD; Jay M. Portnoy, MD; Christopher Randolph, MD;Diane E. Schuller, MD; Sheldon L. Spector, MD; Stephen Tilles, MD; Dana Wallace, MD;Zuhair K. Ballas, MD; James R. Baker, MD; Joseph A. Bellanti, MD; Daniel Ein, MD; andLeslie C. Grammer, MD

TABLE OF CONTENTSI. Preface ................................................................................................................................................................................S2

II. Classification of Recommendations and Evidence ...........................................................................................................S3III. Summary Statements ..........................................................................................................................................................S3IV. Acknowledgments ............................................................................................................................................................S11V. References.........................................................................................................................................................................S12

those who served on the Joint Task Force, is authorized to provide anofficial AAAAI or ACAAI interpretation of these practice parameters. Anyrequest for information about or an interpretation of these practice param-eters by the AAAAI or ACAAI should be directed to the Executive Officesof the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma andImmunology. These parameters are not designed for use by pharmaceuticalcompanies in drug promotion.

Received for publication August 11, 2009; Accepted for publicationAugust 11, 2009.

These parameters were developed by the Joint Task Force on PracticeParameters, representing the American Academy of Allergy, Asthma andImmunology (AAAAI), the American College of Allergy, Asthma andImmunology (ACAAI), and the Joint Council of Allergy, Asthma andImmunology. The AAAAI and the ACAAI have jointly accepted re-sponsibility for establishing “Adverse Reactions to Vaccines.” This is acomplete and comprehensive document at the current time. The medicalenvironment is a changing environment, and not all recommenda-tions will be appropriate for all patients. Because this document incor-porated the efforts of many participants, no single individual, including

VOLUME 103, OCTOBER, 2009 S1

PREFACEThis practice parameter provides a practical, peer-reviewed,evidence-based guide for evaluation and management of pa-tients with suspected allergy to vaccines. This documentcontains detailed and specific guidelines not found in previ-ously published reviews.

The practice parameter offers both general and vaccine-spe-cific recommendations for skin testing to vaccines and compo-nents, serum specific IgE in vitro antibody testing, serologictesting for protective antibody responses to vaccines, vaccine

administration, and avoidance. The guidelines should prove use-ful for primary care physicians and specialists in allergy andimmunology. More importantly, most patients who avoid vac-cination because of allergy concerns will be able to receive theirappropriate vaccinations if this practice parameter is followed.

The 2 key points of the practice parameter are that (1)patients with suspected allergy to vaccines or vaccine com-ponents should be evaluated by an allergist/immunologist and(2) most patients with suspected allergy to vaccines canreceive vaccination safely. With the recent worldwide con-

Figure 1. Suggested approach to suspected adverse reactions to a vaccine.

Note 1. Are nature and timing of reaction consistent with anaphylaxis?Probable Anaphylactic Reaction: reaction occurring within 4 hours of vaccine administration to include signs and/or symptoms from more than 1 ofthe following systems:

– Dermatologic: urticaria, flushing, angioedema, pruritus– Respiratory: rhinoconjunctivitis (red, watery, itchy eyes, stuffy, runny, itchy nose, sneezing), upper airway edema (change in voice, difficulty

swallowing, difficulty breathing), bronchospasm/asthma (cough, wheeze, shortness of breath, chest tightness)– Cardiovascular: hypotension, tachycardia, palpitations, light-headedness, loss of consciousness (Note: hypotension or loss of consciousness with

pallor and bradycardia is much more likely a vasovagal reaction.)– GI: cramping, nausea, vomiting, diarrhea

Possible Anaphylactic Reaction:Signs and/or symptoms from only 1 system (as above)Signs and/or symptoms from more than 1 system (as above) but occurring more than 4 hours after vaccination

Note 2. Skin tests with vaccine and components including gelatin, egg, chicken and/or yeastVaccine skin tests:

– Prick test with full strength vaccine (consider dilution if history of life-threatening reaction)– If prick test with full strength vaccine negative, intradermal test with 0.02 cc vaccine 1:100– Note: Vaccine skin tests may cause false (or clinically irrelevant) positive reactions

Vaccine component/food skin tests:– Prick tests with commercial extracts of whole egg or egg white (influenza and yellow fever vaccines), chicken (yellow fever vaccine) or

Saccharomyces cerevisiae yeast (Hepatitis B vaccine and Human Papillomavirus vaccine)– Prick test with sugared gelatin (e.g. Jell-O®: dissolve 1 teaspoon (5 grams) of gelatin powder in 5 cc normal saline) Vaccines that contain gelatin:

DTaP (some brands), influenza (some brands), Japanese encephalitis, measles, mumps, rabies (some brands), rubella, varicella, yellow fever, zoster

Note 3. If fewer than the recommended number of doses received, consider measuring level of IgG antibodies to immunizing agent. If at a levelassociated with protection from disease, consider withholding additional doses although magnitude and duration of immunity may be less than if alldoses received.

Note 4. Vaccine administration in graded doses:For a vaccine where usual dose is 0.5 ml, administer graded doses of vaccine at 15 minute intervals: 0.05 ml of 1:10 dilution, 0.05 ml of full strength,0.10 ml of full strength, 0.15 ml of full strength, 0.20 ml of full strength. For influenza vaccine in egg-allergic patients, if the egg protein content of thevaccine is known to be < 1.2 �gm/mL, administer 10% of the dose, followed in 30 minutes by the remaining 90%, or as a single dose.

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cerns about H1N1 influenza, interest in the health benefits ofvaccination is greater than ever. Our hope is that this publi-cation will result in safe vaccination for patients with sus-pected allergy to vaccines.

Immunization is perhaps the greatest public health achieve-ment of all time,1 having significantly reduced the morbidityand mortality of many infectious diseases.2 Routine immuni-zation of children, adolescents, and adults provides substan-tial protection from a large number of infectious diseases.The current vaccination schedules for children and adults areavailable at www.cdc.gov/vaccines/recs/schedules.3–5 Pa-tients who have experienced adverse reactions to vaccinesmay unnecessarily be advised to avoid subsequent immuni-zation, which may have important adverse personal and pop-ulation health consequences.6–10 Although there are someadverse reactions to vaccines that constitute absolute contra-indications to administration of future doses, most such re-actions do not preclude subsequent immunization.11 Patientswho have experienced some ill effect after receiving a vac-cine warrant evaluation by an allergist/immunologist. In mostcases, a risk-benefit analysis will favor subsequent immuni-zation (Figure 1).

CLASSIFICATION OF RECOMMENDATIONS ANDEVIDENCECategory of evidenceIa Evidence from meta-analysis of randomized controlled

trialsIb Evidence from at least one randomized controlled trialIIa Evidence from at least one controlled study without ran-

domizationIIb Evidence from at least one other type of quasiexperimen-

tal studyIII Evidence from nonexperimental descriptive studies, such

as comparative studiesIV Evidence from expert committee reports or opinions or

clinical experience of respected authorities or both

Strength of recommendationA Directly based on category I evidenceB Directly based on category II evidence or extrapolated

recommendation from category I evidenceC Directly based on category III evidence or extrapolated

recommendation from category I or II evidenceD Directly based on category IV evidence or extrapolated

recommendation from category I, II, or III evidence

SUMMARY STATEMENTSSummary Statement 1. Mild local reactions and constitutionalsymptoms, such as fever, after vaccinations are common anddo not contraindicate future doses. Rarely, delayed-type hy-persensitivity to a vaccine constituent may cause an injectionsite nodule, but this is not a contraindication to subsequentvaccination. (C)

Local, injection site reactions (swelling, redness, and/orsoreness) and constitutional symptoms, especially fever, are

common after the administration of most vaccines and are notcontraindications to subsequent vaccination.11 Neomycin iscontained in several vaccines.12 For those reporting a de-layed-type hypersensitivity contact dermatitis to neomycin,the only anticipated reaction is a small, temporary papule atthe injection site,13,14 and this is not a contraindication tosubsequent vaccination.11 Delayed-type hypersensitivity tothimerosal has also been reported.15 Although patients with a

Table 1. Levels of Antibody Associated With Protection FromVaccine-Preventable Diseases

VaccineProtective level of IgG

antibody >

Diphtheria 0.1 IU/mL11

Haemophilus influenzae type B 0.15 �g/mL29

Hepatitis A 10 mIU/mL30

Hepatitis B surface antibody 10 mIU/mL31

Measles (rubeola) 120 mIU/mL (PRN titer)32

Polio (inactivated) 1:8 neutralizing antibody titer33

Rabies 0.5 IU/mL (VNA titer)34

Rubella 10 IU/mL80

Tetanus 0.1 IU/mL11

Yellow fever 0.7 IU/mL29

Abbreviations: IU, international units; mIU, milli-international units;PRN, plaque reduction neutralization; VNA, virus-neutralizing anti-bodies.

Table 2. Gelatin Content of Vaccines 2008

Vaccine Gelatin content

DTaP (Tripedia/TriHIBit; SanofiPasteur, Swiftwater,Pennsylvania)

28 �g per 0.5-mL dosea

Influenza (Fluzone; SanofiPasteur)

250 �g per 0.5-mL doseb

Influenza (FluMist; MedimmuneVaccines, Gaithersburg,Maryland)

2000 �g per 0.2-mL doseb

Japanese Encephalitis (JE-VAX;Sanofi Pasteur)

500 �g per 1.0-mL doseb

Measles, Mumps, Rubella(ATTENUVAX, MERUVAXII,MMRII, MUMPSVAX; Merck,Whitehouse Station, NewJersey)

14,500 �g per 0.5-mL doseb

Measles, mumps, rubella,varicella (ProQuad; Merck)

11,000 �g per 0.5-mL doseb

Rabies (RabAvert; Novartis,Emeryville, California)

12,000 �g per 1.0-mL doseb

Typhoid Vaccine Live OralTy21a (VIVOTIF; Berna, CoralGables, Florida)

Capsuleb

Varicella (VARIVAX; Oka/Merck) 12,500 �g per 0.5-mL doseb

Yellow Fever (YF-VAX; SanofiPasteur)

7,500 �g per 0.5-mL dosea

Zoster (ZOSTAVAX; Oka/Merck) 15,580 �g per 0.65-mL doseb

a Sanofi Pasteur, oral communication, September 4, 2009.b Package inserts.

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positive patch test result for thimerosal may have large localreactions to vaccination with thimerosal-containing vac-cines,16,17 most such patients do not.15,18–20 Neither a history ofsuch reactions nor a positive patch test result to thimerosal isa contraindication to future vaccination.11 There is a singlecase report of a generalized pruritic maculopapular rash at-tributed to thimerosal in an influenza vaccine.21 Aluminum-containing vaccines12 rarely cause persistent nodules at theinjection site, possibly because of delayed hypersensitivity orother immune responses to aluminum.22–24

Summary Statement 2. Anaphylactic reactions to vaccinesare estimated to occur at a rate of approximately 1 per milliondoses. There are approximately 235 million doses of vaccinesadministered in the United States each year. (B)

Anaphylaxis after vaccination is rare. The Vaccine SafetyDatalink reviewed the diagnosis codes from medical encoun-ters after the administration of more than 7.5 million doses ofvaccines and estimated the risk of anaphylaxis to be 0.65million to 1.53 per million doses.25 The Centers for DiseaseControl and Prevention (CDC) estimates that there were235,705,179 doses of all vaccines distributed in the UnitedStates in 2007 (Angela Calugar, CDC, written communica-tion, December 19, 2008). Thus, there are approximately 150to 350 cases of vaccine-induced anaphylaxis in the UnitedStates annually. Fatalities from vaccine-induced anaphylaxisare exceedingly rare.26

Summary Statement 3. All serious events occurring aftervaccine administration should be reported to the VaccineAdverse Event Reporting System, even if it is not certain thatthe vaccine was causal. (C)

In 1990, the Vaccine Adverse Event Reporting System(VAERS) was established by the CDC and Food and DrugAdministration (FDA).27 VAERS relies on reporting byhealth care professionals and parents or patients, and allserious events after vaccination should be reported.28 Thesereports of suspected associations between vaccine adminis-tration and adverse events can then be evaluated for strengthof potential causality.

Summary Statement 4. Measuring levels of IgG antibody tothe immunizing agent in a vaccine suspected of causing aserious adverse reaction to determine if they are at protectivelevels can help determine whether or not subsequent dosesare required. (B)

In a patient who has experienced an apparent adversereaction to vaccine yet has received fewer than the recom-mended number of doses, the level of IgG antibodies to theimmunizing agent can be measured to see if it is at a levelassociated with protection from disease. Such levels havebeen established for some, but not all, vaccines (Table1)11,29–34 and are available from many diagnostic laboratories.If so, consideration can be given to withholding additionaldoses, although the magnitude and duration of immunity maybe less than if all doses were received.35,36 Even if the rec-ommended number of doses has already been received or ifprotective antibody levels have already been achieved, eval-uation of the reaction, including skin testing if indicated,should be undertaken as discussed herein.

Summary Statement 5. All suspected anaphylactic reac-tions to vaccines should ideally be evaluated in an attempt todetermine the culprit allergen. (B)

When a patient experiences an apparently IgE-mediatedreaction after an immunization, the patient is often labeled asbeing “allergic” to the vaccine and advised against receivingfuture doses without further investigation. However, this ap-proach should be avoided because it may leave patientsinadequately immunized if they unnecessarily avoid vaccinesto which they are not allergic or if the vaccine could beadministered safely despite their allergy. In addition, notknowing the particular constituent of a vaccine to which thepatient is allergic may pose a risk with future vaccinationsthat contain the same ingredient.

Summary Statement 6. IgE-mediated reactions to vaccinesare more often caused by vaccine components, such as gelatinor egg protein, rather than the immunizing agent itself. (B)

Gelatin is added to many vaccines (Table 2) as a stabilizerand has been shown to be responsible for many anaphylacticreactions to MMR, varicella, and Japanese encephalitis vac-cines.37–40 Vaccine manufacturers in Japan and Germany re-moved gelatin or changed to a less allergenic gelatin with aresultant decrease in allergic reactions.41,42 A history of al-lergy to the ingestion of gelatin should be sought before theadministration of any gelatin-containing vaccine. A negativehistory, however, may not exclude an allergic reaction togelatin injected with the vaccine.38 Gelatin used in vaccines isof either bovine or porcine origin, which are extensively

Table 3. Egg Content of Vaccines

Vaccine Grown in Egg protein contentApproach in egg allergic

patient

Measles and mumps Chick embryo fibroblastcell cultures

Picograms to nanograms Administer in usual manner44–46

Purified chick embryo rabies Chick embryo fibroblastcell cultures

Picograms to nanograms Administer in usual manner109

Influenza (killed injected andlive attenuated nasal)

Chick extraembryonicallantoic fluid

Micrograms Skin test with egg and vaccinebefore administration48,110

Yellow fever Chick embryos Micrograms Skin test with egg and vaccinebefore administration67

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cross-reactive.37,38 There are no published reports of patientsallergic to both gelatin and beef or pork meat.

Measles and mumps vaccines and 1 type of rabies vaccineare grown in chick embryo fibroblast cultures and containnegligible or no egg protein (Table 3).43 Measles or MMRvaccines can be administered to egg allergic children withoutadverse reactions44,45 and can be given to such patients with-out skin testing.46 Egg protein is present in higher amounts inyellow fever and influenza vaccines12 (Table 3) and maycause reactions in egg allergic recipients. Administration ofinfluenza vaccine containing 1.2 �g/mL of egg protein hasbeen safely administered to egg allergic patients, initially in a2-dose protocol (10% of the dose followed in 30 minutes bythe remaining 90% of the dose) and later as a single dose.47

However, the influenza vaccine is newly made every year,and there are variable amounts of egg protein present in anygiven years’ vaccine (as high as 42 �g/mL of egg protein).48

Whether this is sufficient to cause a reaction in an egg allergicpatient is also not known but may pose a risk. Patients can beallergic to heat-labile egg proteins in raw egg and, becausethey tolerate the ingestion of cooked egg, do not think ofthemselves as being egg allergic.49 Thus, the clinical historymay not identify all persons allergic to egg proteins present ininfluenza or yellow fever vaccines. Chicken proteins otherthan those found in chicken egg may be present in yellowfever vaccine and may be responsible for reactions in chickenallergic recipients.50

Hepatitis B vaccines are grown in Saccharomyces cerevi-siae (baker’s yeast or brewer’s yeast) and contain residualyeast protein,12 but adverse reactions to these, if any, appearto be rare.51 Human papillomavirus vaccine may also containresidual yeast protein.52

The rubber in vaccine vial stoppers or syringe plungersmay be either dry natural rubber (DNR) latex or syntheticrubber. Those made with DNR pose a theoretical risk to thepatient who is latex allergic. There is 1 report of an anaphy-lactic reaction in a latex allergic patient after hepatitis Bvaccine attributed to rubber in the stopper.53 A review ofmore than 160,000 VAERS reports found only 28 cases ofpossible immediate-type allergic reactions after receiving aDNR-containing vaccine, and these may have been due toother components.54 The latex content of vaccine packagingis provided in Table 4 and is updated at www.cdc.gov/vaccines/pubs/pinkbook/pink-appendx.htm.55

There is a single report of an immediate-type allergicreaction to a vaccination that was attributed to neomycin.56

However, the patient had a maculopapular (not urticarial)rash to the topical application of neomycin, and no testing forIgE to neomycin was performed. There is a single case reportof an immediate-type reaction that may have been caused bythimerosal in a vaccine.57

However rare, if a patient gives a history of an immediate-type reaction to yeast, latex, neomycin, or thimerosal, it isappropriate to investigate with immediate-type skin testingbefore immunization with a vaccine containing these constit-uents.

Table 5 lists vaccine excipients by vaccine. Updated listsof vaccine excipients by vaccine and by excipient areavailable at www.cdc.gov/vaccines/pubs/pinkbook/pink-appendx.htm.12,58

Summary Statement 7. Patients who have had an apparentanaphylactic reaction after immunization should undergo im-mediate-type allergy skin testing to help confirm that thereaction was IgE mediated and determine the responsiblecomponent of the vaccine. (B)

To determine whether a vaccine was responsible for apatient’s apparent allergic reaction, skin testing with thevaccine should be performed.35,36 The vaccine should first betested by the prick method. Full-strength vaccine can be usedunless the history of the reaction was truly life-threatening, inwhich case beginning even the prick test with dilute vaccineis appropriate. If the full-strength prick test result is negative,with appropriate positive and negative controls, an intrader-mal test with the vaccine diluted 1:100 should be per-formed,59 again with appropriate controls.

As with any skin test reagent, and particularly with mate-rials not standardized for skin testing such as vaccines, false-positive (irritant) results and clinically irrelevant positiveresults may occur. Likewise, false-negative response mayalso be seen. Some patients known to have IgE antibodies tovarious vaccines by in vitro testing or skin testing havenonetheless received the vaccines in the usual manner with-out reaction.47,60–63 Although these findings complicate theinterpretation of vaccine skin tests, if the test result is positivein a patient with a history of an allergic reaction to thevaccine, the patient must be assumed to be allergic. Intrader-mal skin tests with some vaccines, such as tetanus toxoid, canalso induce delayed-type hypersensitivity responses.64

If the suspect vaccine contains gelatin (Table 2), egg(influenza and yellow fever), chicken (yellow fever), or yeast(hepatitis B vaccine and human papillomavirus vaccine), thepatient should also be skin tested for these allergens.35,36 Egg,chicken, and yeast extracts for skin testing are commerciallyavailable. Gelatin can be prepared by dissolving 1 teaspoon(5 g) of any sugared gelatin powder (for example, Jell-O) in5 mL of normal saline to create a prick skin test solution,recognizing that this is not a standardized, validated, FDA-approved method. In vitro assays for specific IgE antibodyare also commercially available for these foods, includinggelatin.

Summary Statement 8. If the intradermal skin test result isnegative, the chance that the patient has IgE antibody to anyvaccine constituent is negligible, and the vaccine can beadministered in the usual manner. It is prudent, nonetheless,in a patient with a history suggestive of an anaphylacticreaction to administer the vaccine under observation withepinephrine and other treatment available. (B)

Although there are no formal studies to evaluate the pos-itive and negative predictive values for intradermal skin testresults in patients who have had apparent allergic reactions tovaccines, the approach is almost certainly sufficiently sensi-tive to identify patients with IgE-mediated reactions to some

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vaccine component. Intradermal skin tests are recommendedwhen increased sensitivity is required for the evaluation ofanaphylaxis.64 There are no reports of patients with negativeintradermal skin test results to a vaccine reacting to subse-quent administration of that vaccine. As with any diagnostictest, the increased sensitivity of intradermal testing likelycomes with some loss of specificity. Thus, although there arereports of patients being safely administered the vaccinesafter negative intradermal skin test results,47,65 there are alsoreports of patients with positive skin test results nonethelessreceiving the vaccines uneventfully.47,63 Dilutions of vaccinesof 1:100 have been demonstrated to be nonirritating.59 Thus,if the skin test results to the vaccine and its ingredients arenegative, particularly at the intradermal level (with the vac-cine diluted 1:100), then it is unlikely that the patient has IgEantibody to any component of the vaccine, and they can be

Table 4. Latex in Vaccine Packaginga

Vaccine Latex

Anthrax (BioThrax) Yes–vialComvax Yes–vialDTaP

Daptacel Yes–vialInfanrix Yes–syringe

No–vialTripedia Yes–vial

DT (generic) Yes–vialHib

HibTITER Yes–vialPedvaxHIB Yes–vialActHIB Yes–diluent vial

No–lyophilized vaccine vialHepatitis A

Havrix Yes–syringeNo–vial

Vaqta Yes–vialYes–syringe

Hepatitis BEngerix-B Yes–syringe

No–vialRecombivax HB Yes–vial

HPV (Gardasil) NoInfluenza

Fluarix Yes–syringeFluvirin NoFluzone NoFluLaval NoAfluria NoFluMist No

Japanese encephalitisJE-Vax NoIxiaro No

Kinrix Yes–syringeNo–vial

MMR (M-M-R II) NoMMRV (ProQuad) NoMeasles (Attenuvax) NoMumps (Mumpsvax) NoRubella (Meruvax II) NoMeningococcal

Menomune Yes–vialMenactra Yes–vial

No–syringePediarix Yes–syringe

No–vialPentacel NoPneumococcal

Pneumovax 23 NoPrevnar Yes–syringe, before lot D46873

No–syringe, lot D46873 andafter

Polio (IPOL) Yes–syringeNo–vial

RabiesImovax Rabies NoRabAvert No

Continued

Table 4. (Continued)

Vaccine Latex

RotavirusRotaTeq NoRotarix Yes–applicator

No–vial and transfer adapterTd

Decavac No–vialNo–syringe

Generic Yes–vialYes–syringe

TdapAdacel NoBoostrix Yes–syringe

No–vialTriHIBit Yes–vialTwinrix Yes–syringe

No–vialTyphoid

Typhim Vi NoVivotif Berna NA

Varicella (Varivax) NoVaccinia (smallpox) (ACAM2000) NoYellow fever (YF-Vax) Yes–vial

Abbreviations: DT, diphtheria and tetanus toxoids (pediatric formula-tion); DTaP, diphtheria and tetanus toxoids and acellular pertussis(pediatric formulation); Hib, Haemophilus influenzae type B; HPV,human papillomavirus; MMRV, measles, mumps, rubella and vari-cella; NA, not applicable; Td, tetanus and diphtheria toxoids (adult/adolescent formulation); Tdap, tetanus and diphtheria toxoids andacellular pertussis (adult/adolescent formulation).a “If a person reports a severe (anaphylactic) allergy to latex, vaccinessupplied in vials or syringes that contain natural rubber should not beadministered unless the benefit of vaccination outweighs the risk fora potential allergic reaction. For latex allergies other than anaphylacticallergies (e.g., a history of contact allergy to latex gloves), vaccinessupplied in vials or syringes that contain dry natural rubber or rubberlatex can be administered.” (Advisory Committee on ImmunizationPractices General Recommendations on Immunization, 2006). Thistable is accurate, to the best of our knowledge, as of June 2009. If indoubt, check the package insert for the vaccine in question.

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Table 5. Excipients Included in US Vaccines, by Vaccinea

Vaccine Contains

Anthrax (BioThrax) Aluminum hydroxide, amino acids, benzethonium chloride, formaldehyde or formalin, inorganic salts andsugars, vitamins

BCG (Tice) Asparagine, citric acid, lactose, glycerin, iron ammonium citrate, magnesium sulfate, potassium phosphateDTaP (Daptacel) Aluminum phosphate, ammonium sulfate, Casamino acid, dimethyl-�-cyclodextrin, formaldehyde or

formalin, glutaraldehyde, 2-phenoxyethanolDTaP (Infanrix) Aluminum hydroxide, bovine extract, formaldehyde or formalin, glutaraldehyde, 2-phenoxyethanol,

polysorbate 80DTaP (Tripedia) Aluminum potassium sulfate, ammonium sulfate, bovine extract, formaldehyde or formalin, gelatin,

polysorbate 80, sodium phosphate, thimerosalb

DTaP/Hib (TriHIBit) Aluminum potassium sulfate, ammonium sulfate, bovine extract, formaldehyde or formalin, gelatin,polysorbate 80, sucrose, thimerosalb

DTaP-IPV (Kinrix) Aluminum hydroxide, bovine extract, formaldehyde, lactalbumin hydrolysate, monkey kidney tissue,neomycin sulfate, polymyxin B, polysorbate 80

DTaP-Hep B-IPV (Pediarix) Aluminum hydroxide, aluminum phosphate, bovine protein, lactalbumin hydrolysate, formaldehyde orformalin, glutaraldehyde, monkey kidney tissue, neomycin, 2-phenoxyethanol, polymyxin B, polysorbate80, yeast protein

DtaP-IPV/Hib (Pentacel) Aluminum phosphate, bovine serum albumin, formaldehyde, glutaraldehyde, MRC-5 DNA and cellularprotein, neomycin, polymyxin B sulfate, polysorbate 80, 2-phenoxyethanol

DT (sanofi) Aluminum potassium sulfate, bovine extract, formaldehyde or formalin, thimerosal (multidose) orthimerosalb (single dose)

DT (Massachusetts) Aluminum hydroxide, formaldehyde or formalinHib (ACTHib) Ammonium sulfate, formaldehyde or formalin, sucroseHib (PedvaxHib) Aluminum hydroxyphosphate sulfateHib/Hep B (Comvax) Amino acids, aluminum hydroxyphosphate sulfate, dextrose, formaldehyde or formalin, mineral salts,

sodium borate, soy peptone, yeast proteinHep A (Havrix) Aluminum hydroxide, amino acids, formaldehyde or formalin, MRC-5 cellular protein, neomycin sulfate, 2-

phenoxyethanol, phosphate buffers, polysorbateHep A (Vaqta) Aluminum hydroxyphosphate sulfate, bovine albumin or serum, DNA, formaldehyde or formalin, MRC-5

cellular protein, sodium borateHep B (Engerix-B) Aluminum hydroxide, phosphate buffers, thimerosal,b yeast proteinHep B (Recombivax) Aluminum hydroxyphosphate sulfate, amino acids, dextrose, formaldehyde or formalin, mineral salts,

potassium aluminum sulfate, soy peptone, yeast proteinHep A/Hep B (Twinrix) Aluminum hydroxide, aluminum phosphate, amino acids, dextrose, formaldehyde or formalin, inorganic

salts, MRC-5 cellular protein, neomycin sulfate, 2-phenoxyethanol, phosphate buffers, polysorbate 20,thimerosal,b vitamins, yeast protein

HPV (Gardasil) Amino acids, amorphous aluminum hydroxyphosphate sulfate, carbohydrates, L-histidine, mineral salts,polysorbate 80, sodium borate, vitamins

Influenza (Afluria) �-Propiolactone, calcium chloride, neomycin, ovalbumin, Polymyxin B, potassium chloride, potassiumphosphate, sodium phosphate, sodium taurodeoxycholate.

Influenza (Fluarix) Egg albumin (ovalbumin), egg protein, formaldehyde or formalin, gentamicin, hydrocortisone, octoxynol-10,�-tocopheryl hydrogen succinate, polysorbate 80, sodium deoxycholate, sodium phosphate, thimerosalb

Influenza (Flulaval) Egg albumin (ovalbumin), egg protein, formaldehyde or formalin, sodium deoxycholate, phosphate buffers,thimerosal

Influenza (Fluvirin) �-Propiolactone, egg protein, neomycin, polymyxin B, polyoxyethylene 9–10 nonyl phenol (triton N-101,octoxynol 9), thimerosal (multidose containers), thimerosalb (single-dose syringes)

Influenza (Fluzone) Egg Protein, Formaldehyde or Formalin, Gelatin, Octoxinol-9 (Triton X-100), Thimerosal (multidosecontainers)

Influenza (FluMist) Chick kidney cells, egg protein, gentamicin sulfate, monosodium glutamate, sucrose phosphate glutamatebuffer

IPV (Ipol) Calf serum protein, formaldehyde or formalin, monkey kidney tissue, neomycin, 2-phenoxyethanol,polymyxin b, streptomycin

Japanese Encephalitis (JE-Vax) Formaldehyde or formalin, gelatin, mouse serum protein, polysorbate 80, thimerosalJapanese Encephalitis (Ixiaro) Aluminum hydroxide, bovine serum albumin, formaldehyde, protamine sulfate, sodium metabisulfiteMeningococcal (Menactra) Formaldehyde or formalin, phosphate buffersMeningococcal (Menomune) Lactose, thimerosal (10-dose vials only)MMR (MMR-II) Amino acid, bovine albumin or serum, chick embryo fibroblasts, human serum albumin, gelatin, glutamate,

neomycin, phosphate buffers, sorbitol, sucrose, vitamins

Continued

VOLUME 103, OCTOBER, 2009 S7

given the vaccine in the usual manner but observed for atleast 30 minutes afterward.35,36

Summary Statement 9. In patients with histories and skintests results consistent with an IgE-mediated reaction to avaccine, who require additional doses of the suspect vaccineor other vaccines with common ingredients, considerationcan be given to administering the vaccine in graded dosesunder observation. (C)

If vaccine or vaccine component skin test results are pos-itive, the vaccine may still be administered, if necessary, ingraded doses (Table 6).46,66,67 For a vaccine where the fullnormal dose volume is 0.5 mL, the patient is first given 0.05

mL of a 1:10 dilution and then given (at 15-minute intervals),0.05 mL of full-strength vaccine, with subsequent doses of0.1 mL, 0.15 mL, and finally 0.2 mL for a cumulative dose of0.5 mL. This or similar protocols have been used successfullyfor the administration of egg-containing vaccines to eggallergic recipients66 and with other vaccines as well.50,68

This procedure in a patient who is presumed to be allergicto the vaccine being administered needs to be performedunder direct medical supervision with emergency medica-tions and equipment to promptly treat an anaphylactic reac-tion should it occur.64 Whether such challenges are under-taken in the office vs hospital or with or without an

Table 5. (Continued)

Vaccine Contains

MMRV (ProQuad) Bovine albumin or serum, gelatin, human serum albumin, monosodium L-glutamate, MRC-5 CellularProtein, Neomycin, Sodium Phosphate Dibasic, Sodium Bicarbonate, Sorbitol, Sucrose, PotassiumPhosphate Monobasic, Potassium Chloride, Potassium Phosphate Dibasic

Pneumococcal (Pneumovax) Bovine protein, phenolPneumococcal (Prevnar) Aluminum phosphate, amino acid, soy peptone, yeast extractRabies (Imovax) Human serum albumin, �-propiolactone, MRC-5 cellular protein, neomycin, phenol red

(phenolsulfonphthalein), vitaminsRabies (RabAvert) Amphotericin B, �-propiolactone, bovine albumin or serum, chicken protein, chlortetracycline, egg

albumin (ovalbumin), EDTA, neomycin, potassium glutamateRotavirus (RotaTeq) Cell culture media, fetal bovine serum, sodium citrate, sodium phosphate monobasic monohydrate,

sodium hydroxide sucrose, polysorbate 80Rotavirus (Rotarix) Amino acids, calcium carbonate, calcium chloride, D-glucose, dextran, ferric (III) nitrate, L-cystine,

L-tyrosine, magnesium sulfate, phenol red, potassium chloride, sodium hydrogenocarbonate, sodiumphosphate, sodium L-glutamine, sodium pyruvate, sorbitol, sucrose, vitamins, xanthan

Td (Decavac) Aluminum potassium sulfate, bovine extract, formaldehyde or formalin, 2-phenoxyethanol, peptone,thimerosalb

Td (Massachusetts) Aluminum hydroxide, aluminum phosphate, formaldehyde or formalin, thimerosal (some multidosecontainers)

Tdap (Adacel) Aluminum phosphate, formaldehyde or formalin, glutaraldehyde, 2-phenoxyethanolTdap (Boostrix) Aluminum hydroxide, bovine extract, formaldehyde or formalin, glutaraldehyde, polysorbate 80Typhoid (inactivated - Typhim Vi) Disodium phosphate, monosodium phosphate, phenol, polydimethylsiloxane,

hexadecyltrimethylammonium bromideTyphoid (oral - Ty21a) Amino acids, ascorbic acid, bovine protein, casein, dextrose, galactose, gelatin, lactose, magnesium

stearate, sucrose, yeast extractVaccinia (ACAM2000) Glycerin, human serum albumin, mannitol, monkey kidney cells, neomycin, phenol, polymyxin BVaricella (Varivax) Bovine albumin or serum, EDTA, gelatin, monosodium L-glutamate, MRC-5 DNA and cellular protein,

neomycin, potassium chloride, potassium phosphate monobasic, sodium phosphate monobasic,sucrose

Yellow fever (YF-Vax) Egg protein, gelatin, sorbitolZoster (Zostavax) Bovine calf serum, hydrolyzed porcine gelatin, monosodium L-glutamate, MRC-5 DNA and cellular

protein, neomycin, potassium phosphate monobasic, potassium chloride, sodium phosphate dibasic,sucrose

Abbreviations: DT, diphtheria and tetanus toxoids (pediatric formulation); DTaP, diphtheria and tetanus toxoids and acellular pertussis (pediatricformulation); Hep A, hepatitis A; Hep B, hepatitis B; Hib, Haemophilus influenzae type B; HPV, human papillomavirus; IPV, inactivated poliovirus;MMRV, measles, mumps, rubella and varicella; Td, tetanus-diphtheria toxoids (adult/adolescent formulation); Tdap, tetanus and diphtheria toxoidsand acellular pertussis (adult/adolescent formulation).a Vaccine Excipient & Media Summary, Part 2. Includes vaccine ingredients (eg, adjuvants and preservatives) and substances used during themanufacturing process, including vaccine-production media, that are removed from the final product and present only in trace quantities. Inaddition to the substances listed, most vaccines contain sodium chloride (table salt). Adapted from Grabenstein JD. ImmunoFacts: Vaccines &Immunologic Drugs. St. Louis, MO: Wolters Kluwer Health; 2009 and individual product package inserts. All reasonable efforts have been madeto ensure the accuracy of this information, but manufacturers may change product contents before that information is reflected here.b The product should be considered equivalent to thimerosal-free products. This vaccine may contain trace amounts (�0.3 �g) of mercury left afterpostproduction thimerosal removal, but these amounts have no biological effect.

S8 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY

intravenous line in place depends on the severity of theoriginal reaction to the vaccine and the patient’s medicalcondition.64

For influenza vaccine in egg allergic patients, if the eggprotein content of the vaccine is known to be 1.2 �g/mL orless, the vaccine can be administered in 2 doses (10% of thedose, followed in 30 minutes by the remaining 90%) or as asingle dose, without prior vaccine skin testing,47 althoughobservation for at least 30 minutes afterward seems prudent(Table 6). Unfortunately, the specific egg protein content ofany given year’s influenza vaccines is not readily available.47

Because of the lot to lot variability in the egg proteincontent of egg-containing vaccines,48 even if an egg allergicpatient has a negative vaccine skin test response and is giventhe vaccine in the usual manner or has a positive vaccine skintest response and is given the vaccine in graded doses, if thepatient needs to be given the vaccine again at a later time, thevaccine skin test, and graded challenge if necessary, wouldneed to be repeated.

Summary Statement 10. Some more serious, and less com-mon, reactions to vaccines require evaluation, but only a feware absolute contraindications to future doses. (B)

In addition to anaphylactic reactions (discussed herein),some vaccines are capable of causing other rare but seriousreactions that might contraindicate the administration of fu-ture doses.11

There was a particular type of influenza vaccine, namely,swine flu vaccine administered in 1976, which was associatedwith an increased risk for Guillain-Barre syndrome (GBS),estimated at 1 additional case per 100,000 vaccinations (overthe annual background rate of 10 to 20 cases per millionadults).69 In subsequent years, influenza vaccines have beencarefully monitored for this possible adverse effect and haveshown no consistent increased risk. If there is any increasedrisk, it is on the order of 1 per million.69,70 A low level of GBScases continues to be reported in temporal association withprevious influenza infection71 and with influenza and othervaccines.72,73 Previous GBS raises the risk of a recurrence ofGBS. Persons who developed GBS within 6 weeks of influ-enza vaccination should avoid subsequent immunization withinfluenza vaccines.69 However, individuals with a history ofGBS unrelated to influenza infection or vaccination whowould benefit from immunization can be vaccinated, partic-

ularly if the influenza infection risk is high or if the infectingstrain is resistant to antiviral therapy.69 The live attenuatedinfluenza vaccine is not recommended in persons with ahistory of GBS simply because it has not been studied forsafety in such persons.69

Measles, mumps, and rubella (MMR) vaccines can causeadverse reactions related to the live viruses they contain.Transient rashes appear in as many as 5% of recipients ofmeasles vaccine, and this probably represents vaccine-in-duced modified measles.32 There is a late-onset fever occur-ring 5 to 12 days after vaccine administration in as many as15% of recipients of the MMR vaccine.32,46,74 As with anyfever in young children, this increases the risk of febrileseizures; however, such seizures do not have any sort oflong-term sequelae.75,76 Recipients of the MMR vaccine canalso have thrombocytopenia, which is usually without anysignificant clinical consequence, but can rarely cause hemor-rhage.26,74,77,78 The rate of thrombocytopenia is much higherwith the disease itself.74 Rubella vaccine can cause acutearthritis in approximately 15% of adult women who receivedthe vaccine.79,80 This may represent a direct infection of thejoints by the vaccine virus but has a questionable associationwith chronic arthritis.79,80 None of these events are contrain-dications to the administration of subsequent doses of MMRvaccine.11

The most serious adverse effect related to pertussis vaccineis termed encephalopathy. This term describes a specific andsevere reaction characterized as an “acute, severe CNS [cen-tral nervous system] disorder occurring within 7 days follow-ing vaccination and generally consisting of major alterationsin consciousness, unresponsiveness, generalized or focal sei-zures that persist more than a few hours, with failure torecover within 24 hours.”26 This event happens with an inci-dence that may actually be 0, meaning that it is not actuallyincreased after vaccination, but to a maximum of 10 permillion doses of diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine.74 This can have permanentneurologic sequela and is an absolute contraindication tofurther pertussis vaccination.11 Pertussis vaccine can causeless severe apparent neurologic events, including febrile sei-zures,75 inconsolable crying,46 and hypotonic-hyporesponsiveepisodes.81 Although these are clearly concerning episodesfor parents to witness, none of them result in permanent

Table 6. Administration of Vaccines in Graded Doses

For a vaccine for which the full normal-dose volume is 0.5 mL,give the following doses at 15-minute intervals as tolerateda

For influenza vaccine in egg allergic patients, if the egg protein contentof the vaccine is known to be �1.2 �g/mL administer as followsb

0.05 mL, 1:10 dilution In 2 doses: 10% of the dose (0.025 mL or 0.05 mL) followed in 30minutes by the remaining 90% of the dose (0.225 mL or 0.45 mL) or0.05 mL, full strength

0.1 mL, full strength In a single dose (0.25 mL or 0.5 mL)0.15 mL, full strength0.2 mL, full strength

a Must be done under direct medical supervision with emergency medications and equipment to promptly treat an anaphylactic reaction shouldit occur.b Observe for at least 30 minutes afterward.

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sequelae, and none of them are contraindications to furtherdoses of these vaccines.11,74,82 Of note is the fact that all theseserious and less serious neurologic events after pertussis-containing vaccines have been significantly reduced sincechanging from the diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP) to the diphtheria and tetanustoxoids and acellular pertussis vaccine (DTaP).46,82–87

Tetanus toxoid often causes patients to develop a largelocal swelling.88 This probably represents an Arthus reactionin patients with preexisting antitetanus antibodies from priorimmunizations who then receive a large injection of antigenin the vaccine. These reactions may cause discomfort but arenot serious. Tetanus toxoid also has some potential associa-tion with Guillain-Barre syndrome and with a rare localneurologic event called brachial neuritis, which involvesshoulder pain followed by weakness.26

Varicella vaccine is another live virus immunization thatcan cause vaccine-induced illness, particularly the appear-ance of varicella lesions. These reactions occur at the injec-tion site in approximately 3% of recipients and in another 3%are more generalized.89 The disease due to coincident naturalexposure may be difficult to distinguish from vaccine-in-duced varicella. A zoster-type rash may rarely appear after avaricella vaccination and may contain either vaccine-strain orwild-type virus.90,91 Although varicella disease (chickenpox)itself can be more severe in children with atopic dermatitis,the varicella vaccine can be safely administered to childrenwith atopic dermatitis without an increased risk of complica-tions.92

A serious adverse effect of yellow fever vaccine is enceph-alitis.93 The risk for this complication is as high as 4 per 1000infants, and for this reason the vaccine is relatively contrain-dicated in this age group. It should not be given to any infantyounger than 4 months and to those younger than 9 monthsonly if their risk from the disease is very high.46 The yellowfever vaccine has recently been associated with a very severeillness in adults. There have been fatalities from multisystem

disease with features strikingly similar to the disease yellowfever itself.94–98 This has occurred in patients who are notknown to be immunocompromised. The cause of these reac-tions is still unknown, but this vaccine should not be given topatients unless they are at risk of acquiring yellow fever,typically by traveling to an area where the disease is endem-ic.99

Summary Statement 11. Pregnant women should not bevaccinated with live vaccines. However, pregnant womenshould be given inactivated influenza vaccine, as well astetanus and hepatitis B vaccine if otherwise indicated. (B)

Because of a theoretical risk of transmitting the live agentto the fetus, pregnant women should not receive live vaccinessuch as MMR, varicella, or live attenuated influenza vac-cine.100 There is an increased risk of hospitalization frominfluenza in pregnancy, and therefore (inactivated) influenzavaccine is specifically indicated in women who will be preg-nant during the influenza season.100 Hepatitis B vaccine andtetanus and diphtheria vaccines should also be administeredto pregnant women if they would otherwise be indicated.100

Summary Statement 12. In general, live vaccines shouldnot be given to persons who are immune compromised be-cause of a risk of generalized infection with the immunizingagent. (B)

Live vaccines (Table 7) are generally contraindicated inpatients with immune suppression, specifically those withsevere humoral or cellular immune deficiency.11,46,101 Thisincludes patients with X-linked agammaglobulinemia, com-mon variable immune deficiency, severe combined immunedeficiency, severe human immunodeficiency virus (HIV) in-fection, leukemia, lymphoma, other malignant neoplasms, orpatients requiring treatment for these or other conditions withtreatment modalities that impair immune responses, such ashigh-dose corticosteroids (2 weeks of daily treatment withprednisone, 20 mg or 2 mg/kg or equivalent per day). Thereare, however, exceptions even to this general rule that im-mune compromised patients should not receive live viralvaccines.11,46,101 For example, the MMR vaccine should begiven to HIV-infected children and adults if they have onlymild or moderate disease. Similarly varicella vaccine shouldbe given to mildly HIV-infected children.

Summary Statement 13. Specific vaccines or vaccination ingeneral have been purported to have long-term consequences,including atopy, autism, and multiple sclerosis. Epidemio-logic studies have not supported such associations. (B)

There are a number of controversies related to long-termconsequences of particular vaccines or of vaccination ingeneral. There have been claims that receiving childhoodvaccinations increases the likelihood of developing atopicdisease, autism, diabetes, or multiple sclerosis. The associa-tions have all been extensively evaluated using many appro-priate research methods and epidemiologic studies, and norelationship between vaccinations and any of these outcomeshas been demonstrated in these studies.102–106 There has beenparticular concern about thimerosal, which was previouslyused as a preservative in vaccines. Although studies have

Table 7. Live vs Killed Vaccines

Live vaccines Killed vaccines

Bacille Calmette-Guerin (BCG)Influenza (intranasal)

Diphtheria, tetanus and acellularpertussis (DTaP, Tdap)

Measles-mumps-rubella (MMR) Diphtheria-tetanus (DT, Td)Oral poliovirus (OPV Hepatitis ARotavirus Hepatitis BTyphoid (oral) Hib conjugatesVaccinia (smallpox) Human papillomavirus (HPV)Varicella Inactivated poliovirus (IPV)Yellow fever Influenza (injectable)Zoster Japanese encephalitis

MeningococcalMeningococcal conjugatePneumococcalPneumococcal conjugateRabiesTyphoid (injectable)

S10 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY

failed to support any adverse effect from thimerosal exposurein vaccines,107,108 all routinely recommended vaccines forinfants and children in the United States are now availableonly as thimerosal-free formulations or contain only traceamounts of thimerosal, with the exception of some inacti-vated influenza vaccines. Inactivated influenza vaccine forpediatric use is available as a thimerosal preservative-con-taining formulation, a trace thimerosal-containing formula-tion, and a thimerosal-free formulation.46

ACKNOWLEDGMENTSPublished Practice Parameters of the Joint Task Force onPractice Parameters for Allergy & Immunology include thefollowing:

1. Practice parameters for the diagnosis and treatment ofasthma. J Allergy Clin Immunol. 1995;96(suppl):S707-S870.

2. Practice parameters for allergy diagnostic testing. AnnAllergy. 1995;75:543–625.

3. Practice parameters for the diagnosis and managementof immunodeficiency. Ann Allergy. 1996;76:282–294.

4. Practice parameters for allergen immunotherapy. J Al-lergy Clin Immunol. 1996;98:1001–1011.

5. Disease management of atopic dermatitis: a practiceparameter. Ann Allergy. 1997;79197–211.

6. The diagnosis and management of anaphylaxis. J Al-lergy Clin Immunol. 1998;101(suppl):S465-S528.

7. Algorithm for the diagnosis and management of asthma:a practice parameter update. Ann Allergy. 1998;81:415–420.

8. Diagnosis and management of rhinitis: parameter doc-uments of the Joint Task Force on Practice Parameters inAllergy, Asthma and Immunology. Ann Allergy. 1998;81(suppl):S463-S518.

9. Parameters for the diagnosis and management of sinus-itis. J Allergy Clin Immunol. 1998;102(suppl):S107-S144.

10. Stinging insect hypersensitivity: a practice parameter. JAllergy Clin Immunol. 1999;103:963–980.

11. Disease management of drug hypersensitivity: a prac-tice parameter. Ann Allergy. 1999;83(suppl):S665-S700.

12. Diagnosis and management of urticaria: a practiceparameter. Ann Allergy. 2000;85(suppl):S521-S544.

13. Allergen immunotherapy: a practice parameter. AnnAllergy. 2003;90(suppl):SI-S540.

14. Symptom severity assessment of allergic rhinitis: part I.Ann Allergy. 2003;91:105–114.

15. Disease management of atopic dermatitis: an updatedpractice parameter. Ann Allergy. 2004;93:S1-S21.

16. Stinging insect hypersensitivity: a practice parameterupdate. J Allergy Clin Immunol. 2004;114;:869–86.

17. The diagnosis and management of anaphylaxis: anupdated practice parameter. J Allergy Clin Immunol. 2005;115:S483-S523.

18. Practice parameter for the diagnosis and managementof primary immunodeficiency. Ann Allergy. 2005;94:S1-S63.

19. Attaining optimal asthma control: a practice parameter.J Allergy Clin Immunol. 2005;116:S3–11.

20. The diagnosis and management of sinusitis: a practiceparameter update. J Allergy Clin Immunol. 2005;116:S13–47.

21. Food allergy: a practice parameter. Ann Allergy. 2006;96:S1–68.

22. Contact dermatitis: a practice parameter. Ann Allergy.2006;97:S1-S38.

23. Allergen immunotherapy: a practice parameter secondupdate. J Allergy Clin Immunol. 2007;120:S25–85.

24. Bernstein IL, Li JT, Bernstein DI, et al. Allergy diag-nostic testing: an updated practice parameter. Ann Allergy.2008;100:S1-S147.

25. Wallace D, Dykewicz M, Bernstein DI, et al. Diagnosisand management of rhinitis: an updated practice parameter. JAllergy Clin Immunol. 2008;121:S1-S84.

These parameters are also available on the Internet athttp://www.jcaai.org

The Joint Task Force has made a concerted effort toacknowledge all contributors to this parameter. If any con-tributors have been excluded inadvertently, the Task Forcewill ensure that appropriate recognition of such contributionsis made subsequently.

These parameters were developed by the Joint Task Forceon Practice Parameters, representing the American Academyof Allergy, Asthma and Immunology; the American Collegeof Allergy, Asthma and Immunology; and the Joint Councilof Allergy, Asthma and Immunology.

Chief Editors, John M. Kelso, MD, Division of Allergy,Asthma and Immunology, Scripps Clinic, San Diego, Cali-fornia; and James T. Li, MD, PhD, Professor of Medicine,Mayo Clinic College of Medicine, Rochester, Minnesota;Task Force Reviewers, David I. Bernstein, MD, Departmentof Clinical Medicine, Division of Immunology, University ofCincinnati College of Medicine, Cincinnati, Ohio; JoannBlessing-Moore, MD, Department of Immunology, StanfordUniversity Medical Center, Palo Alto, California; Linda Cox,MD, Department of Medicine, Nova Southeastern University,Davie, Florida; David A. Khan, MD, Department of InternalMedicine, University of Texas Southwestern Medical Center,Dallas, Texas; David M. Lang, MD, Allergy/ImmunologySection, Division of Medicine, Cleveland Clinic Foundation,Cleveland, Ohio; Richard A. Nicklas, MD, Department ofMedicine, George Washington Medical Center, Washington,DC; John Oppenheimer, MD, Department of Internal Medi-cine, New Jersey Medical School, Morristown, New Jersey;Jay M. Portnoy, MD, Section of Allergy, Asthma & Immu-nology, The Children’s Mercy Hospital, University of Mis-souri-Kansas City School of Medicine, Kansas City, Mis-souri; Christopher Randolph, MD, Center for Allergy,Asthma and Immunology, Yale Affiliated Programs Water-bury Hospital, Waterbury, Connecticut; Diane E. Schuller,MD, Department of Pediatrics, Pennsylvania State Univer-sity, Milton S. Hershey Medical College, Hershey, Pennsyl-vania; Sheldon L. Spector, MD, Department of Medicine,UCLA School of Medicine, Los Angeles, California; StephenA. Tilles, MD, Department of Medicine, University of Wash-

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ington School of Medicine, Redmond, Washington; DanaWallace, MD, Department of Medicine, Nova SoutheasternUniversity, Davie, Florida; Invited Reviewers, James Baker,MD, Professor of Medicine and Bioengineering, Director ofMichigan Nanotechnology Institute for Medicine and Biolog-ical Sciences, Chief Division of Allergy, Ann Arbor, Mich-igan; Zuhair K. Ballas, MD, Professor and Director Divisionof Allergy, Department of Internal Medicine, University ofIowa, Iowa City, Iowa; Joseph A. Bellanti, MD, Professor ofPediatrics, Microbiology and Immunology, Director of Inter-national Center for Interdisciplinary Studies of Immunology,Georgetown University Medical Center, Washington, DC;Daniel Ein, MD, Clinical Professor and Chief, Division ofAllergy, George Washington University School of Medicine,Washington, DC; Leslie C. Grammer, MD, Director BazleyAsthma and Allergy Center, Professor Feinberg School ofMedicine, Northwestern University, Chicago, Illinois.

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